Trial Title:
Selinexor in Combination With MTX+Ritu to Treat R/R CNSL
NCT ID:
NCT05698147
Condition:
Central Nervous System Lymphoma
Conditions: Official terms:
Lymphoma
Rituximab
Methotrexate
Conditions: Keywords:
Relapse refractory
Selinexor
ATG-010
Primary Central Nervous System Lymphoma（PCNSL）
Secondary Central Nervous System Lymphoma（SCNSL）
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Selinexor
Description:
Selinexor dose escalation: 60,80,100mg respectively on day 1,8,15,22 for 28 days cycles,
and dose expansion at the RP2D of Selinexor.
PR patients after induction treatment will continue ATG-010 maintenance up to 1 year or
until disease progression, intolerable toxicity, death.
Arm group label:
X-MTX-Ritu
Other name:
ATG-010
Intervention type:
Drug
Intervention name:
Rituximab
Description:
Rituximab 375 mg/m2 intravenous infusion d1, every 28 days for 6 cycles during
combination induction treatment.
Arm group label:
X-MTX-Ritu
Other name:
RiTUXimab Injection
Intervention type:
Drug
Intervention name:
Methotrexate
Description:
high-dose Methotrexate 3.5 g/m2 intravenous infusion d1, every 28 days for 6 cycles
during combination induction treatment.
Arm group label:
X-MTX-Ritu
Other name:
MTX
Summary:
This is a single-arm and open-label study to explore X+MTX+Ritu (ATG-010, Methotrexate,
Rituximab) regimen in Relapse refractory PCNSL patients. Approximately 30 patients will
be enrolled in the study. In dose escalation phase, patients with Relapse refractory
PCNSL will be treated with X+MTX+Ritu regimen and escalating doses of oral ATG-010 weekly
in a 3+3 design. Then a phase 2 expansion at the recommended dose level based on phase 1b
trial will be conducted to evaluate the efficacy, safety and tolerability.
Detailed description:
In dose escalation phase, patients with Relapse refractory PCNSL will be treated with
X+MTX+Ritu regimen （Methotrexate 3.5 g/m2, d1; Rituximab 375 mg/m2, d0）and escalating
doses of oral ATG-010 weekly in a 3+3 design. ATG-010 dose level (DL) 1, 2 and 3 are 60,
80 and 100mg respectively respectively on day 1,8,15,22 for 28-days cycle.
The phase 2 expansion at the recommended dose level based on phase 1b trial. The total 6
cycles, 28 days per cycle . And, Subjects participating in the study will undergo a
screening period（up to 21days）, a treatment period, and a follow-up period. The screening
period is a maximum of 21 days before treatment period, And will be followed by 6 cycles
of combination treatment（28 days per cycle）.
partial remission(PR) patients after induction treatment will continue ATG-010
maintenance up to 1 year or until disease progression, intolerable toxicity, death.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patients must meet all of the following inclusion criteria to be eligible to enroll
in this study:
1. Participants must be able to understand and be willing to sign a written
informed consent document.
2. Men and woman who are 18-75 years old on the day of consenting to the study.
3. Histologically documented PCNSL and SCNSL secondary to histologically
documented systemic diffuse large B-cell lymphoma (DLBCL).
4. Patients must have relapsed/refractory PCNSL or relapsed/refractory SCNSL.
5. Patients must have response or remain stable disease for 2 months to prior
methotrexate-based regimen.
6. Patients who had prior autologous hematopoietic stem cell transplantation are
eligible.
7. Patients with parenchymal lesions must have unequivocal evidence of disease
progression on imaging (MRI of the brain or head CT) 28 days prior to cycle1
day 1(C1D1). For patients with leptomeningeal disease only, CSF cytology must
document lymphoma cells.
8. Participants must have an Eastern Cooperative Oncology Group performance status
of 0-3.
9. Participants must have adequate bone marrow and organ function shown by:
1. Absolute neutrophil count (ANC) ≥ 1.0 x 10^9/L
2. Platelets ≥ 75 x 10^9/L and no platelet transfusion within the past 14
days prior to study registration c Hemoglobin (Hgb) ≥ 8 g/dL and no red
blood cell (RBC) transfusion within the past 14 days prior to study
registration
10. International Normalized Ratio (INR) ≤ 1.5 and PTT (aPTT) ≤ 1.5 times the upper
limit of normal.
11. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times
the upper limit of normal.
12. Serum bilirubin ≤ 1.5 times the upper limit of normal; or total bilirubin ≤ 3
times the upper limit of normal with direct bilirubin within the normal range
in patients with well documented Gilbert Syndrome.
13. Calculated creatinine clearance(CrCl)≥50ml/min using the Cockcroft-Gault
equation or 24-hour urine collection.
14. Life expectancy of > 3 months.
Exclusion Criteria:
1. Patients with SCNSL actively receiving treatment for extra-CNS disease are excluded.
2. Lymphoma patients with only intraocular involvement.
3. Pathological diagnosis of PCNSL is T-cell lymphoma.
4. Patients with disease progression within 6 months of prior methotrexate-containing
regimen.
5. patients only had received stereotactic radiation therapy as prior treatment.
6. Patients have received chemotherapy, monoclonal antibodies or targeted anticancer
therapy within 21 days or 5 half-lives, whichever is shorter, prior to C1D1.
7. Patients with active, unstable cardiovascular diseases, fits any of the following:
1. myocardial infarction within 6 months prior to the study enrollment
2. unstable angina within 3 months prior to the study enrollment
3. Uncontrolled clinically-significant conduction abnormalities (e.g., ventricular
tachycardia, ventricular fibrillation, etc.)
4. Congestive heart failure (CHF) of New York Heart Association (NYHA) ≥ Grade 3
5. Echocardiography showing left ventricular ejection fraction less than 50%
8. Uncontrolled active infection within 1 week prior to the first dose of study drug.
9. Known active hepatitis B, or C infection or HIV infection; Note: Hepatitis B virus
(HBV) surface antigen (HBsAg) and or hepatitis B core antibody-positive but
undetectable HBV DNA or Hepatitis C virus (HCV) antibody positive but hepatitis C
virus RNA undetectable are allowed.
10. Active GI dysfunction interfering with the ability to swallow tablets, or any GI
dysfunction that could interfere with absorption of study treatment.
11. Prior exposure to a selective inhibitor of nuclear export(SINE) compound, including
selinexor.
12. Serious, active psychiatric, or medical conditions which, in the opinion of the
Investigator, could interfere with study treatment.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
The First Affiliated Hospital Of Anhui Medical University
Address:
City:
Hefei
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Jian Ge, Ph.D
Facility:
Name:
Beijing Tiantan Hospital, Capital Medical University
Address:
City:
Beijing
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Wenbin Li, Ph.D
Phone:
+8615301377998
Email:
neure55@126.com
Facility:
Name:
The First Affiliated Hospital Of Fujian Medical University
Address:
City:
Fuzhou
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Zhiyong Zeng, Ph.D
Facility:
Name:
Oncology Department of The First Affiliated Hospital of Zhengzhou University
Address:
City:
Zhengzhou
Zip:
450052
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Mingzhi Zhang, PhD
Phone:
13838565629
Email:
mingzhi_zhang@126.com
Investigator:
Last name:
Mingzhi Zhang, PhD
Email:
Principal Investigator
Facility:
Name:
Department of Hematology, Huashan Hospital, Fudan University
Address:
City:
Shanghai
Zip:
200040
Country:
China
Status:
Recruiting
Contact:
Last name:
Tong Chen
Phone:
+862152887102
Email:
chentong@fudan.edu.cn
Contact backup:
Last name:
Yan Yuan
Phone:
+862152888283
Email:
yuanyan@fudan.edu.cn
Start date:
August 3, 2023
Completion date:
December 31, 2026
Lead sponsor:
Agency:
Tong Chen, MD
Agency class:
Other
Collaborator:
Agency:
Antengene Corporation
Agency class:
Industry
Source:
Huashan Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05698147
